CYP17 Lyase and Androgen Receptor Inhibitor Treatment With Seviteronel Trial (INO-VT-464-006; NCT02580448)

Breast Cancer Clinical Trial

— CLARITY-01  

Official title:

A Phase 1/2 Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Seviteronel in Subjects With Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580448
• Other study ID #: INO-VT-464-CL-006
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2015
• Est. completion date: January 2019

Study information

• Verified date: January 2019
• Source: Innocrin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is to determine the safety, pharmacokinetics, pharmacodynamics and efficacy and activity of seviteronel, a lyase-selective inhibitor of CYP17, in patients with advanced breast cancer.

Description:

This is an open-label, Phase 1/2 study of seviteronel in subjects with TNBC or ER +/HER2 normal unresectable locally advanced breast cancer. Only women will be enrolled in Phase 1 and both men and women enrolled into their respective cohorts in Phase 2. There will be a dose confirmation Phase 1 portion of the study to establish the recommended Phase 2 dose (RP2D) for women with breast cancer using a non-stratified, combined cohort of women with TNBC or ER+ BC. Cohort expansion will occur in Phase 2 at the RP2D confirmed/established in Phase 1 using separate TNBC and ER+ cohorts. The Phase 2 portion of the study is divided into three parallel cohorts:

Cohort 1: Female TNBC Subjects Cohort 2: Female ER+ Subjects Cohort 3: Male ER+ BC or TNBC Subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Each subject eligible to participate in this study must meet or have all the following criteria:

1. Is 18 years of age or older.

2. Can provide written informed consent or have their legal representatives provide written informed consent

3. Have documented histological or cytological evidence of invasive cancer of the breast, defined by one of the following:

• ER+ breast cancer, defined as positive if = 1% by IHC and HER2 normal, defined as IHC 0-1+ or IHC 2+(and FISH<2), or FISH < 2.0

• TNBC, defined as ER-/PgR- if 0 % by IHC and HER2 normal, defined as IHC 0-1+ or IHC 2+(and FISH<2), or FISH < 2.0

4. ECOG PS of 0 or 1 for Females, 0, 1, or 2 for Males.

5. Undergoing or willing to undergo gonadal suppression:

• Female subjects with ER+/HER2 normal tumors must be post-menopausal defined by local practice. Ovarian suppression with a LHRH analogue to achieve cessation of regular menses is allowed on study

• Male subjects must be undergoing or willing to undergo gonadal suppression whilst on study drug and continue with the LHRH analogue for the duration of the study

6. Subjects must have adequate hematopoietic function as evidenced by:

• WBC = 3,000/µl

• ANC = 1,500/µl

• Platelet count = 100,000/µl

• HGB = 9 g/dl and not transfusion dependent

7. Adequate liver function, including all the following:

• Total serum bilirubin =2.0 x ULN unless the subject has documented Gilbert syndrome;

• Aspartate and alanine aminotransferase (AST & ALT) =3.0 x ULN or =5.0 x ULN if subject has liver metastasis;

• Alkaline phosphatase =3.0 x ULN or =5 x ULN in case of bone metastasis and/or hepatic metastasis

8. Subjects must have adequate renal function as evidenced by a serum creatinine of = 2.0 mg/dl.

9. Potassium (K+) =3.5 mEq/L

10. Women of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours of C1D1.

11. Women of child-bearing potential and male subjects with a female partner of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period and for 3 months after final study drug administration i. Two acceptable forms of birth control include:

1. Condom (barrier method of contraception), and 2. One of the following:

1. Oral, injected or implanted hormonal contraception

2. Placement of an intrauterine device (IUD) or intrauterine system (ISU)

3. Additional barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

4. Vasectomy or surgical castration = 6 months prior to Screening. 12. Able to swallow study medication 13. Able to comply with study requirements

Exclusion Criteria

1. Received any investigational agent within 5 half-lives of the agent in question; if the half-life is not known, = 28 days of C1D1.

2. Received palliative radiotherapy = 2 weeks of C1D1

3. Received any other therapeutic treatment for breast cancer = 2 weeks of C1D1, except for hormonal therapies.

4. Symptomatic CNS metastases.

5. History of another invasive malignancy = 3 years of C1D1.

6. A QTcF interval >470 msec on the Screening ECG. If the ECG QTcF interval is >470 msec, then the mean QTcF of a triplicate ECGs can be used and if the mean is <470 msec, the subject may be enrolled.

7. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, atrial fibrillation with rapid ventricular response, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place).

8. Class III or IV Congestive Heart Failure (CHF) as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months

9. Initiated a bone modifying agent (e.g. denosumab) = 28 days of C1D1.

10. Any medical condition that could preclude their participation in the study, pose an undue medical hazard, or which could interfere with the interpretation of the study results.

11. A history of seizure = 2 years of C1D1 or those who require prophylactic anti-seizure medications.

12. A history of loss of consciousness or transient ischemic attack = 12 months before C1D1.

13. Known active HIV, Hepatitis B, or Hepatitis C infections.

14. Known or suspected hypersensitivity to seviteronel, or any components of the formulation.

15. Any other condition which in the opinion of the investigator would preclude participation in the study.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Neoplasms
• Breast Neoplasms, Male
• Cancer of the Breast
• ER+ Breast Cancer
• Male Breast Cancer
• Metastatic Breast Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Seviteronel
Seviteronel given daily with evening meal in 28 day cycles

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Wallace Tumor Institute- University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Charleston Hematology and Oncology Associates	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center - Oncology Research	Charlotte	North Carolina
United States	Oncology Hematology Care, Inc	Cincinnati	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Mary Crowley Cancer Research Centers	Dallas	Texas
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	The Center for Cancer and Blood Disorders (Fort Worth)	Fort Worth	Texas
United States	US Oncology	Fort Worth	Texas
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	SCRI - HCA Midwest Division	Kansas City	Kansas
United States	Precision Cancer Research/Brig Center for Cancer Care and Survivorship, LLC	Knoxville	Tennessee
United States	Rocky Mountain Cancer Centers	Lakewood	Colorado
United States	University of Louisville Hospital / James Brown Cancer Center	Louisville	Kentucky
United States	Masonic Cancer Center	Minneapolis	Minnesota
United States	SCRI Tenessee Oncology Nashville	Nashville	Tennessee
United States	Memorial Sloan Kettering	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Cancer Network/Oncology Associates PC	Omaha	Nebraska
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	OHSU Knight Cancer Institute	Portland	Oregon
United States	Florida Cancer Specialists- North	Saint Petersburg	Florida
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Maryland Oncology Hematology	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Innocrin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate efficacy of seviteronel as measured by clinical benefit rate at 16 weeks (CBR16) for female subjects with TNBC.		Duration of Study
Primary	Estimate efficacy of seviteronel as measured by clinical benefit rate at 24 weeks (CBR24) for female subjects with ER+ BC.		Duration of Study
Primary	Estimate efficacy of seviteronel as measured by CBR16 for all male BC subjects.		Duration of Study
Secondary	Describe the pharmacokinetics of seviteronel	Area under the curve concentration verses time curve and Peak Plasma Concentration	At least monthly over the first eight 28-day cycles
Secondary	Estimate efficacy of seviteronel as measured by the overall response rate (ORR) based on RECIST 1.1		At least monthly over the first eight 28-day cycles
Secondary	Estimate efficacy of seviteronel as measured by progression-free survival (PFS)		At least monthly over the first eight 28-day cycles
Secondary	Describe the safety profile of seviteronel		Duration of the study
Secondary	Compare the safety profile of seviteronel with or without concurrent glucocorticoid administration		Duration of the study
Secondary	Compare the CBR16 with or without concurrent glucocorticoid administration for female subjects with TNBC		Duration of the study